ABSTRACT
Obesity is associated with the production of inflammatory cytokines that are implicated in insulin resistance (IR), and if not addressed, can lead to type 2 diabetes (T2D). The role of the immune system in skeletal muscle (SM) inflammation and insulin sensitivity is not yet well characterized. As SM IR is an important determinant of glycaemia, it is critical that the muscle-immune phenotype is mapped to help design interventions to target T2D. This systematic review synthesized the evidence for SM macrophage content and phenotype in humans and murine models of obesity, and the association of muscle macrophage content and phenotype with IR. Results were synthesized narratively, as we were unable to conduct a meta-analysis. We included 28 studies (n=10 human, n=18 murine), and all studies detected macrophage markers in SM. Macrophage content was positively associated with IR. In humans and mice, there was variability in muscle macrophage content and phenotype in obesity. Overall certainty in the evidence was low due to heterogeneity in detection methods and incompleteness of data reporting. Macrophages are detected in human and murine SM in obesity and a positive association between macrophage content and IR is noted; however, the standardization of markers, detection methods, and reporting of study details is warranted to accurately characterize macrophages and improve the potential for creating specific and targeted immune-based therapies in obesity.
Subject(s)
Diabetes Mellitus, Type 2/immunology , Inflammation/immunology , Insulin Resistance/physiology , Macrophages/physiology , Muscle, Skeletal/immunology , Obesity/immunology , Animals , Diabetes Mellitus, Type 2/etiology , Diabetes Mellitus, Type 2/physiopathology , Disease Models, Animal , Glucose Clamp Technique , Humans , Inflammation/physiopathology , Macrophage Activation/immunology , Mice , Obesity/complications , Obesity/physiopathologyABSTRACT
BACKGROUND: Adolescent idiopathic scoliosis (AIS) is the most common form of scoliosis in children, and its cause remains unknown. The Immune-metabolic CONnections to Scoliosis (ICONS) Study was designed to elucidate the potential mechanisms by which immune system-paraspinal muscle crosstalk contributes to the development of AIS. In this report, we document the evaluation of ICONS Study feasibility. METHODS: This study was conducted at a tertiary pediatric academic center in Hamilton, Ontario, Canada. We included boys and girls, aged 10-17 years with a diagnosis of AIS requiring corrective spinal surgery. Exclusion criteria included patients on high-dose steroids, immunosuppressive therapy, anti-thrombotic medications, those with an active infection for 15 days before participation, autoimmune disease, pregnancy, and patients who were unwilling to consent.Pre-determined feasibility criteria included permission to approach participants and recruitment rates of 80%, consenting of at least 80% of participants to provide biological samples, 90% or higher case report form and questionnaire completion, resources to be sufficient in at least 80% of recruitments, and the ability to successfully collect and process 80% or more of the biological samples needed for this study. RESULTS: Between August 2013 and October 2014, we identified 32 potential participants with AIS, but had the resources to approach only 16, of which 12 (75%) agreed to be approached by the research team, and all consented to participate. Of the 12 participants recruited, 11 questionnaire packages and muscle biopsies (91.7% for each objective) were collected, while other biological samples (serum, plasma, whole blood for DNA and RNA processing, urine) were collected from all participants. CONCLUSIONS: The ICONS study protocols and procedures are feasible. However, recruitment rates were less than predicted. For the full study, we plan on prolonging the recruitment phase and the inclusion of additional centers to achieve recruitment targets.
ABSTRACT
OBJECTIVES: The current global rates of obesity and type 2 diabetes are staggering. In order to implement effective management strategies, it is imperative to understand the mechanisms of obesity-induced insulin resistance and diabetes. Macrophage infiltration and inflammation of the adipose tissue in obesity is a well-established paradigm, yet the role of macrophages in muscle inflammation, insulin resistance and diabetes is not adequately studied. In this systematic review, we will examine the evidence for the presence of macrophages in skeletal muscle of obese humans and mice, and will assess the association between muscle macrophages and insulin resistance. We will identify published studies that address muscle macrophage content and phenotype, and its association with insulin resistance. We will search MEDLINE/PubMed, EMBASE, and Web of Science for eligible studies. Grey literature will be searched in ProQuest. Quality assessment will be conducted using the Systematic Review Centre for Laboratory Animal Experimentation risk of bias Tool for animal studies. RESULTS: The findings of this systematic review will shed light on immune-metabolic crosstalk in obesity, and allow the consideration of targeted therapies to modulate muscle macrophages in the treatment and prevention of diabetes. The review will be published in a peer-reviewed journal and presented at conferences.